This proposal describes a series of fundamental and applied immunologic investigations focusing on the pathologic consequences of immunologic malfunction. This multidisciplinary program project includes: Studies of the etiologic agents, particularly viruses and autoantigens which may initiate pathogenic immune responses. Attempts to define the fundamental abnormalities of the lymphoreticular system which predispose to lupus type autoimmunity in several murine strains. Investigation of the nature of B cell activation and the cellular events involved in induction, maintenance and termination of immunologic unresponsiveness. Study of the ability of viruses to alter host gene products present on the surfaces of infected cells and the consequences of such alterations in reactions with antibody, complement, and lymphoid cells reactive with cell surface and viral antigens. Further definition of the alternative complement pathway via isolation, mapping, and sequencing of nephritic factor followed by in vivo studies of its action. Further evaluation and characterization of substances activating the complement system, such as bacterial products and endotoxins, fragments of the lipopolysaccharide molecule, viruses, polyanions and cations, as well as immunoglobulins. Examination of the effects of activating factor B on the functions of murine macrophages snd human monocytes including their ability to phagocytize, secrete proteinases, pinocytose and express membrane 5' nucleotidase activity. Determination of the significance of the cleavage of Hageman factor at sites 1 and 2 will be made, particularly in relation to the possibility that site 1 activation is responsible for initiating the clotting system while site 2 activation results in kinin formation and fibrinolytic activity. Investigation of a variety of nonimmunologic host factors such as RE function and the production of and responsiveness to vasoactive amines in the localization and disposition of immune complexes. Quantitation and characterization of antigen-antibody complexes in the circulation of rats grafted with skin or kidney and of dams impregnated by allogeneic males.